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Muscular dystrophy includes a diverse group of inherited muscle diseases characterized by wasting and weakness of skeletal muscle. Mutations in dysferlin are linked to two clinically distinct muscle diseases, limb-girdle muscular dystrophy type 2B and Miyoshi myopathy, but the mechanism that leads to muscle degeneration is unknown. Dysferlin is a homologue(More)
Plasma membrane disruptions are resealed by an active molecular mechanism thought to be composed, in part, of kinesin, CaM kinase, snap-25, and synaptobrevin. We have used HRP to mark the cytoplasmic site of a mechanically induced plasma membrane disruption. Transmission electron microscopy revealed that vesicles of a variety of sizes rapidly (s) accumulate(More)
On demand, rapid Ca(2+)-triggered homotypic and exocytic membrane-fusion events are required to repair a torn plasma membrane, and we propose that this emergency-based fusion differs fundamentally from other rapid, triggered fusion reactions. Emergency fusion might use a specialized protein and organelle emergency response team that can simultaneously(More)
Muscle and bone anabolism and catabolism are tightly coupled during growth, development, and aging, yet the cellular and molecular mechanisms linking these two tissues are not well understood. Here we show that FGF-2 and IGF-1, two growth factors known to play a major role in regulating bone formation, are localized to muscle fibers along the muscle-bone(More)
PURPOSE Elevated plasma homocysteine has been implicated in glaucoma, a vision disorder characterized by retinal ganglion cell death. The toxic potential of homocysteine to ganglion cells is known, but the mechanisms are not clear. A mechanism of homocysteine-induced death of cerebral neurons is via N-methyl-D-aspartate (NMDA) receptor overstimulation,(More)
A microneedle puncture of the fibroblast or sea urchin egg surface rapidly evokes a localized exocytotic reaction that may be required for the rapid resealing that follows this breach in plasma membrane integrity (Steinhardt, R.A,. G. Bi, and J.M. Alderton. 1994. Science (Wash. DC). 263:390-393). How this exocytotic reaction facilitates the resealing(More)
A break in the integrity of the plasma membrane immediately compromises this structure's essential role as a barrier, and this can kill the affected cell. Yet animal cell plasma membranes, unprotected by a cell wall, are highly vulnerable to mechanically induced disruption. Moreover, many tissue environments generate and receive " physiological " levels of(More)
Severe vitamin E deficiency results in lethal myopathy in animal models. Membrane repair is an important myocyte response to plasma membrane disruption injury as when repair fails, myocytes die and muscular dystrophy ensues. Here we show that supplementation of cultured cells with α-tocopherol, the most common form of vitamin E, promotes plasma membrane(More)
We describe a simple method for loading exogenous macromolecules into the cytoplasm of mammalian cells adherent to tissue culture dishes. Culture medium was replaced with a thin layer of fluorescently labeled macromolecules, the cells were harvested from the substrate by scraping with a rubber policeman, transferred immediately to ice cold media, washed,(More)